Ovarian Cancer Stem Cell–Like Side Populations Are Enriched Following Chemotherapy and Overexpress EZH2

作者: Siân Rizzo , Jenny M. Hersey , Paul Mellor , Wei Dai , Alessandra Santos-Silva

DOI: 10.1158/1535-7163.MCT-10-0788

关键词:

摘要: Platinum-based chemotherapy, with cytoreductive surgery, is the cornerstone of treatment advanced ovarian cancer; however, acquired drug resistance a major clinical obstacle. It has been proposed that subpopulations tumor cells stem cell-like properties, such as so-called side populations (SP) overexpress ABC transporters, can sustain growth drug-resistant cells, leading to recurrence following chemotherapy. The histone methyltransferase EZH2 key component polycomb-repressive complex 2 required for maintenance cell state, and overexpression implicated in shorter survival cancer patients. We observed higher percentage SP ascites from patients have relapsed chemotherapy compared chemonaive patients, consistent selection this subpopulation during platinum-based Furthermore, ABCB1 (P-glycoprotein) are consistently overexpressed non-SP patients' cells. siRNA knockdown leads loss models, reduced anchorage-independent growth, vivo. Together, these data support role drug-resistant, tumor-sustaining cancers undergoing As such, an important target anticancer development.

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